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In this study, we examined the effect of GSK\u20103 inhibition on the production of TNF\u2010\u03b1 by neutrophils. In the murine air pouch model of inflammation, lithium chloride (LiCl) amplified TNF\u2010\u03b1 release. In lipopolysaccharide\u2010stimulated human neutrophils, GSK\u20103 inhibitors mimicked the effect of LiCl, each potentiating TNF\u2010\u03b1 release after 4 h, in a concentration\u2010dependent fashion, by up to a 3\u2010fold increase (ED\n                    <jats:sub>50<\/jats:sub>\n                    of 1 mM for lithium). LiCl had no significant effect on cell viability. A positive association was revealed between GSK\u20103 inhibition and prolonged activation of the p38\/MNK1\/eIF4E pathway of mRNA translation. Using lysine and arginine labeled with stable heavy isotopes followed by quantitative mass spectrometry, we determined that GSK\u20103 inhibition markedly increases (by more than 3\u2010fold)\n                    <jats:italic>de novo<\/jats:italic>\n                    TNF\u2010\u03b1 protein synthesis. Our findings shed light on a novel mechanism of control of TNF\u2010\u03b1 expression in neutrophils with GSK\u20103 regulating mRNA translation and raise the possibility that lithium could be having a hitherto unforeseen effect on inflammatory diseases.\u2014Giambelluca, M. S., Bertheau\u2010Mailhot, G., Laflamme, C., Rollet\u2010Labelle, E., Servant, M. J., Pouliot, M. TNF\u2010\u03b1 expression in neutrophils and its regulation by glycogen synthase kinase\u20103: a potentiating role for lithium.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 3679\u20133690 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-251900","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T00:35:43Z","timestamp":1399422943000},"page":"3679-3690","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["TNF\u2010\u03b1 expression in neutrophils and its regulation by glycogen synthase kinase\u20103: A potentiating role for lithium"],"prefix":"10.1096","volume":"28","author":[{"given":"Miriam S.","family":"Giambelluca","sequence":"first","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec Quebec City Quebec Canada"},{"name":"Faculty of Medicine Universit\u00e9 Laval Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Bertheau\u2010Mailhot","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec Quebec City Quebec Canada"},{"name":"Faculty of Medicine Universit\u00e9 Laval Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Laflamme","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec Quebec City Quebec Canada"},{"name":"Faculty of Medicine Universit\u00e9 Laval Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Rollet\u2010Labelle","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec Quebec City Quebec Canada"},{"name":"Faculty of Medicine Universit\u00e9 Laval Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc J.","family":"Servant","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al Montr\u00e9al Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pouliot","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec Quebec City Quebec Canada"},{"name":"Faculty of Medicine Universit\u00e9 Laval Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2960015"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb05715.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2001.100.re12"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01269.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.1.27"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9128-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.10.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.09.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.10.009"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000494"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1221"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052658"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8455"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(99)00064-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3899\/jrheum.090210","article-title":"Immunopathogenesis of psoriasis and pharmacological perspectives","volume":"83","author":"Loffredo S.","year":"2009","journal-title":"J. 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